| First Author | Manicone AM | Year | 2009 |
| Journal | Am J Pathol | Volume | 175 |
| Issue | 6 | Pages | 2319-31 |
| PubMed ID | 19893044 | Mgi Jnum | J:155322 |
| Mgi Id | MGI:4413505 | Doi | 10.2353/ajpath.2009.090101 |
| Citation | Manicone AM, et al. (2009) Matrilysin (Matrix Metalloproteinase-7) regulates anti-inflammatory and antifibrotic pulmonary dendritic cells that express CD103 (alpha(E)beta(7)-integrin). Am J Pathol 175(6):2319-31 |
| abstractText | The E-cadherin receptor CD103 (alpha(E)beta(7)-integrin) is expressed on specific populations of pulmonary dendritic cells (DC) and T cells. However, CD103 function in the lung is not well understood. Matrilysin (MMP-7) expression is increased in lung injury and cleaves E-cadherin from injured lung epithelium. Thus, to assess matrilysin effects on CD103-E-cadherin interactions in lung injury, wild-type, CD103(-/-), and Mmp7(-/-) mice, in which E-cadherin isn't cleaved in the lung, were treated with bleomycin or bleomycin with nFMLP to reverse the defect in acute neutrophil influx seen in Mmp7(-/-) mice. Pulmonary CD103(+) DC were significantly increased in injured wild-type compared with Mmp7(-/-) mice, and CD103(+) leukocytes showed significantly enhanced interaction with E-cadherin on injured wild-type epithelium than with Mmp7(-/-) epithelium in vitro and in vivo. Bleomycin-treated CD103(-/-) mice had persistent neutrophilic inflammation, increased fibrosis, and increased mortality compared with wild-type mice, a phenotype that was partially recapitulated in bleomycin/nFMLP-treated Mmp7(-/-) mice. Soluble E-cadherin increased IL-12 and IL-10 and reduced IL-6 mRNA expression in wild-type bone marrow-derived DC but not in CD103(-/-) bone marrow-derived DC. Similar mRNA patterns were seen in lungs of bleomycin-injured wild-type, but not CD103(-/-) or Mmp7(-/-), mice. In conclusion, matrilysin regulates pulmonary localization of DC that express CD103, and E-cadherin cleavage may activate CD103(+) DC to limit inflammation and inhibit fibrosis. |
